Novel Mechanism of Fetal Hepatocyte Injury in Congenital Alloimmune Hepatitis Involves the Terminal Complement Cascade
Novel Mechanism of Fetal Hepatocyte Injury in Congenital Alloimmune Hepatitis Involves the Terminal Complement Cascade
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DOI：
10.1002/hep.23581
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发表时间：
2010-06-01
期刊：
影响因子：
13.5
通讯作者：
Whitington, Peter F.
中科院分区：
文献类型：
--
作者：
Pan, Xiaomin;Kelly, Susan;Whitington, Peter F.
有证据表明，大多数新生儿血色素沉着症（NH）是妊娠同种免疫胎儿肝损伤的表型表达。妊娠同种免疫疾病是由特异性反应性免疫球蛋白G通过胎盘诱导的，通常涉及通过经典途径激活胎儿补体，导致膜攻击复合物（MAC）的形成，作为细胞损伤的效应。我们检查了NH病例、非NH肝病病例和无肝病婴儿的肝脏标本，以确定它们是否能提供MAC参与肝细胞损伤的证据。切片用抗人C5b-9复合物（MAC组装中形成的末端补体级联（TCC）新抗原）进行免疫染色。NH病例的胎儿肝损伤与肝细胞的严重损失有关。在所有检查的NH病例中，大多数剩余的肝细胞显示TCC新抗原的强烈染色，而非NH肝病病例的肝细胞显示可变的光染色。NH组含TCC新抗原的肝细胞比例远高于非NH组，且两组间无重叠。两组的研究结果表明，肝细胞具有保护MAC的机制，包括其排泄的胆道途径。结论：所有已证实的NH病例含有TCC新抗原，远远超过其他新生儿肝脏疾病的病例，这一发现表明，单一过程，即先天性同种免疫肝炎，是NH的主要原因。mac介导的先天性同种免疫肝炎的同种免疫损伤是一种新的肝损伤机制，是母体适应性免疫和胎儿先天免疫相互作用的结果。(肝脏病学51:2061 2010;2068)
Evidence suggests that most neonatal hemochromatosis (NH) is the phenotypic expression of gestational alloimmune fetal liver injury. Gestational alloimmune diseases are induced by the placental passage of specific reactive immunoglobulin G and often involve the activation of fetal complement by the classical pathway leading to the formation of membrane attack complex (MAC) as the effector of cell injury. We examined liver specimens from cases of NH, from cases of non-NH liver disease, and from infants without liver disease to determine if they would provide evidence that MAC is involved in hepatocyte injury. Sections were immunostained with anti-human C5b-9 complex, the terminal complement cascade (TCC) neoantigen formed in the assembly of MAC. Fetal liver injury in NH cases is associated with a severe loss of hepatocytes. In all NH cases examined, most remaining hepatocytes showed intense staining for TCC neoantigen, whereas hepatocytes in non-NH liver disease cases showed variable light staining. The percentage of hepatocytes containing TCC neoantigen in NH was much greater than that in non-NH liver disease, and there was no overlap between the groups. Findings in both groups suggest that hepatocytes have mechanisms to protect against MAC, including a biliary pathway for its excretion. Conclusion: The finding that all cases of proven NH contained TCC neoantigen far in excess of cases of other neonatal liver diseases suggests that a single process, namely congenital alloimmune hepatitis, is the principal cause of NH. MAC-mediated alloimmune injury in congenital alloimmune hepatitis is a novel mechanism of liver injury that results from an interplay of maternal adaptive immunity and fetal innate immunity. (HEPATOLOGY 2010;51:2061-2068)